The error-prone replication of RNA viral genomes makes them notorious for their ability to evolve resistance to selective agents rapidly and effectively. For cytoplasmic positive-strand RNA viruses such as poliovirus, other picornaviruses such as foot-and-mouth disease virus, and more distantly related flaviviruses such as Dengue and West Nile viruses, an infection started by a single genome can quickly become heterogeneous, even in the first infected cell. Therefore, a progeny genome containing a newly generated mutation that could confer a selective advantage must replicate and package in the context of an essentially polyploid infection in order to propagate.
There is a need in the art for anti-viral agents that, when administered, do not give rise to drug-resistant virus in the early stages of viral infection.